1. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 ‘Add-on’ tests: a national audit of current practice John Monaghan Royal Derby Hospital & Chesterfield Royal Hospital

2. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Reflective testing Adding on tests to help –Establish diagnosis –Assist patient management –Reduce time to diagnosis –Reduce cost in repeating sampling Based on Clinical judgement Ethics

3. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Guidance – General medical council GMC. Consent: Patients and Doctors Making Decisions Together, 2008 statement * Note for pathologists and radiologists: there may be times when uncertainty about a diagnosis can only be resolved by investigations which were not specifically ordered as part of the original request for testing. If these investigations appear to fall outside the scope of the original consent given by the patient, or there are particular sensitivities around the condition for which the pathologist or radiologist wishes to test, they must contact the treating doctor and establish whether further discussion with,and consent from, the patient is necessary before proceeding.

4. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Guidance – Royal Collage of Pathologist Guidance on consent for the processing and analysis of clinical samples following an initial consultation November 2008 4.2 If the investigation is to be extended beyond the list of tests that have been specifically discussed, then those responsible must satisfy themselves that either: the course of action lies within the overall nature of the problem, or the information revealed by the results available requires immediate further investigation because of the clinical importance of the situation and obtaining further explicit consent from the patient is impractical, and the investigation is in the best interests of the patient. 4.3 Patients have the right to exclude the performance of specific tests.

5. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Published Evidence Paterson JR et al (2004) – Clinical effectiveness Srivastava R et al (2010) - Clinical effectiveness Darby D et al (2006) – User questionaire Menlowe M et al (2010) - Guidance

6. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Trent audit group Audited with questions based on work published by Darby et al Audit 2008, re-audited Jan 2010 Tests added at authorising Results commented with suggested test HormoneTumour markers General ChemistryGenetic test TroponinPregnancy test

7. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Audit Responses 344 responses Clinical Biochemistry & Immunology 77 medical staff 217 Scientist 2 Technical

8. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Answers A – Add-on Test B – Discuss with requesting clinician before adding on the test C – Add a comment about suggesting the test D – Comment on results without suggesting further testing E – Take no further action F – Other (please specify). This includes automated or reflex testing.

9. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 1 35-year-old female with fatigue. No previous results. Free T4 – 26.0 pmol/L (RR 10-24 pmol/L) TSH - <0.05 miu/L (RR 0.35-5.5 miu/L) When considering hyperthyroidism would you add on a Free T3?

10. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 1 - Responses Other comments : Reflex tested, add on Total T3, local audit showed no extra information

11. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 2 23-year-old female with Amenorrhoea. Gonadotrophins and hormones were normal over the previous 12 months but no clinical details. No urine or serum pregnancy test had been carried out. LH - <0.5 IU/L FSH - <0.5 IU/L Would you add on serum HCG?

12. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 2 - Responses Other comments : Add on TFTs, E2, Prolactin.

13. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 3 21-year-old male. Request form gives the clinical details as erectile dysfunction. No previous results. Testosterone – 7 nmol/L (RR 10-34 nmol/L) Would you add on LH/FSH to determine if this Is primary or secondary hypogonadism?

14. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 3 responses Other comments : Add SHBG, TFTs, Prolactin, repeat in am. Suggest endocrine referral.

15. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 4 84-year-old female. Request form gives Clinical details as “TATT”. Thyroid function tests had been measured 12 months before and TSH was within the reference range. No other tests were done. Free T4 – 8.0 pmol/L (RR 10-24 pmol/L) TSH – 0.35 miu/L (RR 0.35-5.5 miu/L) Would you add on further pituitary hormones to confirm hypopituitarism?

16. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 4 - Responses Other comments : Discussion of poor fT4 assays. Discuss ?clinically hypopit. Add T3 to check for T3-treatment.

17. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 5 54-year-old male with no clinical details on the form nor any previous results. Request was for a U&E but the sample was noted to be lipaemic. Would you add on triglycerides/lipids?

18. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 5 - Responses Other comments : Several laboratories reflex this test. One lab used to reflex but had a complaint from a patient.

19. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 6 68-year-old male with clinical details on the form as “anaemia”. No previous results for several years. Bilirubin – 19 μmol/L (RR range <20 μmol/L) Alkaline phosphatase – 158 IU/L (RR 56 – 119 IU/L) ALT – 40 IU/L (RR <40 IU/L) Total protein – 106 g/L (RR 60 – 80 g/L) Albumin – 40 g/L (RR 35 – 50 g/L) Globulin – 66 g/L Would you add on electrophoresis and/or immunoglobulins?

20. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 6 - Responses Other comments : Not all labs do total protein/Globulins on profiles. Some would use CRP before deciding on adding on globs.

21. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 7 56-year-old female with no clinical details. Previous results showed a steadily increasing ALP. Bilirubin – 18 μmol/L (RR <20 μmol/L) Alkaline phosphatase – 203 IU/L (RR 53 – 141 IU/L) ALT – 32 IU/L (RR <40 IU/L) Total protein – 78 g/L (RR 60 – 80 g/L) Albumin – 42 g/L (RR 35 – 50 g/L) Globulin – 26 g/L If this is not on your routine profile of requests would you add on serum gamma glutamyl-transferase to help determine origin of raised ALP?

22. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 7 - Responses Others comments: GGT part of profile, some prefer to do ALP-isoenzyme electrophoresis as next line of investigation.

23. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 8 78-year-old male, clinical details “Bone pain”. Previous results showed a steadily increasing ALP but with glutamyltransferase within the reference range. 25-OH Vitamin D had been analysed recently and suggested adequate intake. Bilirubin – 20 μmol/L (RR <20 μmol/L) Alkaline phosphatase – 548 IU/L (RR 56 – 119 IU/L) ALT – 32 IU/L (RR <40 IU/L) Total protein – 79 g/L (RR 60 – 80 g/L) Albumin – 40 g/L (RR 35 – 50 g/L) Globulin – 39 g/L Would you add on PSA to check for prostate cancer?

24. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 8 - Responses Other comments : Several would check calcium & PTH, many would want to discuss to exclude Pagets. One respondent suggested other malignancies.

25. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 9 GP patient, 42-year-old male has clinical details “Chest Pain”. No previous results. Sample arrived in the lab the same day as being taken. Request form asked for CK. Creatinine Kinase – 560 IU/L (RR 10-200 IU/L) Would you add on troponin?

26. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 9 - Responses Other comments (Medics): Phone GP to discuss. Other comments (Scientist): Phone GP. Add AST/LDH, some sites do not offer to primary care, Troponin carried out before CK with those clinical details.

27. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 10 45-year-old female with clinical details Borderline TFTs”. Previous results 6 and 12 months earlier were similar to those shown below. Free T4 – 12.0 pmol/L (RR 10-24 pmol/L) TSH – 9.0 miu/L (RR 0.35-5.5 miu/L) Would you add on anti-thyroid peroxisomal antibodies?

28. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 10 - Responses Other comments : Refer to regional guidelines. Contrasting views on use/misuse of TPO antibodies

29. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 11 50-year-old male with previously deranged LFTs. U&E and full blood count gave all results within reference ranges. Ferritin was requested. Ferritin – 981 μg/L (RR 10 – 290) Would you add on a transferrin saturation or TIBC (form indicates this is a fasting sample)?

30. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 11 - Responses Other comments : Ferritin authorised by Haematology

31. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 12 The GP sends a further fasting sample two weeks later with the following results: Iron – 37 μmol/L (RR 12-25) Transferrin – 24.4 μmol/L Transferrin Saturation - 76% (RR 20-45) If the appropriate sample type was available would you add on HFE genotyping?

32. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 12 - Responses Other comments : Refer to Haemochromatosis specialist, need to obtain consent. Tests not carried out in Biochemistry.

33. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 13 40-year-old male with clinical details “Liver disease”. Electrophoresis showed significantly decreased alpha-1 proteins. Would you add on alpha-1-antitrypsin/phenotyping?

34. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 13 - Responses Other comments : Many comments would add-on A 1 AT to determine activity as first line.

35. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 14 18 year old female with clinical details “Diarrhoea”. No previous results. Alkaline phosphatase – 65 IU/L (RR 35 – 104 IU/L) Calcium – 2.01 mmol/L (RR 2.20-2.60 mmol/L) Adjusted calcium - 2.07 mmol/L (RR 2.20-2.60 mmol/L) Phosphate – 0.80 mmol/L (RR 0.70 – 1.40 mmol/L) Total protein – 70 g/L (RR 60 – 80 g/L) Albumin – 37 g/L (RR 35 – 50 g/L) Globulin – 33 g/L Would you add on magnesium?

36. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 14 - Responses Other comments : Add potassium, reflex testing for magnesium. Add PTH.

37. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 15 50 year old male with clinical details “Anaemia”. Full blood count results showed patient has a macrocytic anaemia. Vitamin B12 – 167 ng/L (RR >190 ng/L) Serum Folate – 12 ng/ml (RR >2.5 ng/ml) Ferritin – 78 μg/L (RR 20 to 320 μg/L) Would you add on intrinsic factor antibodies?

38. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 15 - Responses Other comments : Suggest anti-TTG, parietal cell antibodies, Methylmalonic acid investigation. Results authorised by haematology.

39. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 16 18 year old male with clinical details “New diabetic”. HbA1c analysis shows patient has a haemoglobin variant. Would you add on haemoglobin variant electrophoresis?

40. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Question 16 - Responses Other comments : Lots of comments. Depends if variant interferes with HbA1c peak. Sample referred for assay which gives accurate result. Refer to Haematology consultant. Carry out fructosamine.

41. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Choices affected by additional cost to requestor Comments : Most responses state GP on block contract. Cost not seen by requestor. Genetic tests considered very expensive so these limited

42. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Are any of the above scenarios formally covered in a written SOP or authorising guidelines? Most laboratories had 3-4 protocols. One had 8 protocols

43. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Summary Hormone and general chemistry testing added on if useful to answer question Tumour marker PSA is not added on but commented, myeloma screening is added on Genetic testing HFE, Hb variant is not generally added on but alpha-1 anti-trypsin is Difficult to determine processes in cross-discipline tests e.g. IFA, Ferritin, TIBC Most respondents comment if test is not added on

44. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 No responses Those in clinical biochemistry field that didn’t comment were consistent. 15% medics and 25% of scientist. Why? No enough time to fill out audit? Not normal practice to comment? Test not authorised by individual? Inexperience? ‘E’ responders were not consistent

45. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 What next? Publish Raise awareness Ask GPs what they want Should there be a box for GP to stop reflex of any test?

46. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 Acknowledgements Dr Adam Gerrard, Birmingham Children’s Hospital Dr Paul Masters, Chesterfield Royal Hospital Professor Eric Kilpatrick, Hull Royal Infirmary National audit group Trent Health Chemical Pathology Panel and Audit Group Mr Mike Lester, ACB

47. Derby Hospitals NHS Foundation Trust National Audit Meeting – Add-on tests 24/09/10 References Paterson JR et al. Reflective testing: how useful is the practice of adding on tests by laboratory clinicians. J Clin Pathol. 2004, 57 : 273-275 Darby D et al. Reflective testsing – what do our service users think? Ann Clin Biochem 2006, 43, 361-368 GMC Consent: patients and doctors making decisions together. 2008 RCPath Guidance on consent for the processing and analysis of clinical samples following an initial consultation. 2 nd edn. 2008 Menlowe M. Guidance on consent for the processing and analysis of clinical samples following an initial consultation. Buttetin of the royal college of pathologist 2010, 149, 57-58 Srivastava R et al Reflex and reflective testing: efficiency and effectiveness of adding on laboratory tests Ann Clin Biochem 2010,47,223-227